Sars-2 ORF1b jakson osalta proteiiniksi muuttuminen vaatii ohjelmoidun ribosomaalisen l frameshifting- tapahtuman (kehyssiirron). Merafloksasiini.

 KEHYSSIIRROSTA  ja kehyssiirron estäjäproteiinista SHIFTLESS 

SHIFTLESS geeni on SHFL(19p13.2). Tämä kuuluu  ihmisen luonnollisen immuunipuolustusken  jäseniin ja  se voi kohdistaa vaikutuksensa viruksiin, jotka ovat ihmisille vaarallisia ja vaativat  replikaatioonsa  kehyssiirtotapahtuman ( Frameshifting). 

GeneCards: https://www.genecards.org/cgi-bin/carddisp.pl?gene=SHFL&keywords=SHFL

Aliases for SHFL Gene

• GeneCards Symbol: SHFL ²
• Shiftless Antiviral Inhibitor Of Ribosomal Frameshifting ^{2 3 5}
• RyDEN ^{2 3 4 5}
• IRAV ^{2 3 4 5}
• SFL ^{2 3 4 5}
• FLJ11286 ^{2 4 5}
• C19orf66 ^{3 4 5}
• Shiftless Antiviral Inhibitor Of Ribosomal Frameshifting Protein ^{3 4}

• Interferon-Regulated Antiviral Protein ^{3 4}
• Repressor Of Yield Of Dengue Virus ^{2 3}
• Repressor Of Yield Of DENV Protein ^{3 4}
• Shiftless ^{2 3}
• Interferon-Regulated Antiviral Gene ²
• Chromosome 19 Open Reading Frame 66 ²
• UPF0515 Protein C19orf66 ³
• RYDEN ⁴

 

Kommenttini:  Lisätietoa  (1) tästä proteiinista: SITAATTI 20.12.2021.

Entrez Gene Summary for SHFL Gene

• This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]

GeneCards Summary for SHFL Gene

SHFL (Shiftless Antiviral Inhibitor Of Ribosomal Frameshifting) is a Protein Coding gene. Diseases associated with SHFL include Dengue Virus and Japanese Encephalitis.

UniProtKB/Swiss-Prot Summary for SHFL Gene

• Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a variety of mRNAs from viruses, such as HIV1, and cellular genes, such as PEG10. Interacts with the -1PRF signal of target mRNA and translating ribosomes and causes premature translation termination at the frameshifting site (PubMed:30682371). Regulates HIV1 GAG-POL expression by inhibiting -1PRF (PubMed:30682371). Exhibits antiviral activity against dengue virus (DENV) and can inhibit the replication of all DENV serotypes. May block the protein translation of DENV RNA via its association with cellular mRNA-binding proteins and viral RNA. Interrupts also Zika virus replication by promoting viral NS3 degradation via a lysosome-dependent pathway (PubMed:32150556). Can also limit the replication of hepatitis C virus (HCV) by restricting formation of viral replication organelle, West Nile virus (WNV), Chikungunya virus (CHIKV), herpes simplex virus type 1 (HHV-1), herpes virus type 8 (HHV-8) and human adenovirus (PubMed:26735137, PubMed:27974568, PubMed:30944177, PubMed:32294532). Binds nucleic acids with a higher affinity for ssRNA and ssDNA than for dsDNA (PubMed:27974568).

  • SHFL_HUMAN,Q9NUL5
• Isoform 4 does not inhibit programmed ribosomal frameshifting (-1PRF). Does not bind to ribosomes.

  • SHFL_HUMAN,Q9NUL5

Kommentti: Lisätietoa (2). esimerkki   kehykssiirrosta Sars-2 viruksessa ORF1b  kohdassa. Kehyssiirron  estävää lääkeainetta  etsitty.

https://www.pnas.org/content/118/26/e2023051118

 Abstract

Translation of open reading frame 1b (ORF1b) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires a programmed −1 ribosomal frameshift (−1 PRF) promoted by an RNA pseudoknot. The extent to which SARS-CoV-2 replication may be sensitive to changes in −1 PRF efficiency is currently unknown. Through an unbiased, reporter-based high-throughput compound screen, we identified merafloxacin, a fluoroquinolone antibacterial, as a −1 PRF inhibitor for SARS-CoV-2. Frameshift inhibition by merafloxacin is robust to mutations within the pseudoknot region and is similarly effective on −1 PRF of other betacoronaviruses. Consistent with the essential role of −1 PRF in viral gene expression, merafloxacin impedes SARS-CoV-2 replication in Vero E6 cells, thereby providing proof-of-principle for targeting −1 PRF as a plausible and effective antiviral strategy for SARS-CoV-2 and other coronaviruses.

(  Artikkeliin liittyy kuva  kehyssiirtokohdasta ja selitys sen periaatteesta).. 

Upon the entry of SARS-CoV-2 into host cells, the first set of viral proteins are translated from the long (>21-kb) open reading frame ORF1ab, which takes up approximately two-thirds of the viral genome (Fig. 1A) (1, 2). The ORF1ab-encoded polyprotein is subsequently processed into 16 individual nonstructural proteins (nsp) by two proteases, PLpro/nsp3 and 3CLpro/nsp5. The 3′ half of ORF1ab, ORF1b, encodes a variety of enzymes critical for viral transcription and replication, including an RNA-dependent RNA polymerase (RdRp/nsp12), an RNA helicase (Hel/nsp13), a proofreading exoribonuclease and N7-guanosine methyltransferase (ExoN/nsp14), an endonuclease (NendoU/nsp15), and a 2′-O-methyltransferase (nsp16). In all coronaviruses, translation of ORF1b requires a programmed −1 ribosomal frameshift (−1 PRF) (3).